TGF-beta promotes immune deviation by altering accessory signals of antigen-presenting cells.
Macrophages incubated with OVA in the presence of TGF-beta2 induce immune deviation in vivo (impaired delayed hypersensitivity and IgG2a Ab production) when injected into naive, syngeneic mice. OVA-specific TCR transgenic naive T cells (DO11.10 T cells) produce Th1-type cytokines when stimulated in vitro with OVA-pulsed peritoneal exudate cells (PEC), but if PEC are first treated with TGF-beta2 and then pulsed with OVA, the T cells secrete Th2-type cytokines instead. In this study, we investigated the mechanisms that are involved in the modified Ag-presenting functions of macrophages by TGF-beta2 pretreatment. We have found that: 1) TGF-beta2 impaired the capacity of PEC to produce IL-12 and to express CD40; 2) reduced CD40 expression on TGF-beta2-treated PEC impaired IL-12 production when the cells were cocultured with DO11.10 T cells; 3) the failure of TGF-beta2-treated PEC to stimulate DO11.10 T cells to secrete IFN-gamma was due to their impaired IL-12 production. From these results, we conclude that TGF-beta2 treatment impairs the ability of macrophages to produce IL-12 and to express CD40. As a consequence, TGF-beta2-treated PEC fail to promote development of pT cells toward the Th1 phenotype.
Takeuchi
M
M
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Alard
P
P
Streilein
J W
JW
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D002478:Cells, Cultured; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000906:Antibodies; D019013:CD40 Antigens; D008024:Ligands; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma